NADPH oxidase of human neutrophils. Subcellular localization and characterization of an arachidonate-activatable superoxide-generating system.

Clark, Robert A.; Leidal, Kevin G.; Pearson, Doran W.; Nauseef, William M.

doi:10.1016/s0021-9258(18)61312-2

Cited by 254 publications

(28 citation statements)

References 77 publications

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“…A few years later, the existence of a NADPH oxidase [5], exhibiting a 100-fold selectivity of NADPH over NADH [6,7], was demonstrated and a myeloperoxidase (MPO) was shown to contribute to the ROS production resulting in antimicrobial activity [8]. This phenomenon was finally referred to as the oxidative burst.…”

Section: Nox Family Of Nadph Oxidases: Discovery Of the Phagocytic Enzyme And History Of Noxmentioning

confidence: 99%

NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology

et al. 2021

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The reactive oxygen species (ROS)-producing enzyme NADPH oxidase (NOX) was first identified in the membrane of phagocytic cells. For many years, its only known role was in immune defense, where its ROS production leads to the destruction of pathogens by the immune cells. NOX from phagocytes catalyzes, via one-electron trans-membrane transfer to molecular oxygen, the production of the superoxide anion. Over the years, six human homologs of the catalytic subunit of the phagocyte NADPH oxidase were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with the NOX2/gp91phox component present in the phagocyte NADPH oxidase assembly itself, the homologs are now referred to as the NOX family of NADPH oxidases. NOX are complex multidomain proteins with varying requirements for assembly with combinations of other proteins for activity. The recent structural insights acquired on both prokaryotic and eukaryotic NOX open new perspectives for the understanding of the molecular mechanisms inherent to NOX regulation and ROS production (superoxide or hydrogen peroxide). This new structural information will certainly inform new investigations of human disease. As specialized ROS producers, NOX enzymes participate in numerous crucial physiological processes, including host defense, the post-translational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. These diversities of physiological context will be discussed in this review. We also discuss NOX misregulation, which can contribute to a wide range of severe pathologies, such as atherosclerosis, hypertension, diabetic nephropathy, lung fibrosis, cancer, or neurodegenerative diseases, giving this family of membrane proteins a strong therapeutic interest.

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Section: Nox Family Of Nadph Oxidases: Discovery Of the Phagocytic Enzyme And History Of Noxmentioning

confidence: 99%

NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology

et al. 2021

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“…Upon cellular activation, the regulatory subunits relocate from the cytosol to the plasma membrane or to the phagosomal membrane and induce enzymatic activity (Clark et al 1990). Biochemical analysis established that the cytosolic proteins p47, p67 and Rac were sufficient to reconstitute superoxide production in a cell-free system containing purified flavocytochrome b558, provided that an anionic amphiphile was used as an activator (Bromberg & Pick 1984;Clark et al 1987). Further studies indicated that the activation of the oxidase in the cell-free system absolutely required p67 phox and Rac but not p47 phox , suggesting that p67 phox functions as 'activator' to initiate electron flow across gp91 phox , while p47 phox and Rac act as 'organizers' of the p67 phox -gp91 phox interaction (Nisimoto et al 1999).…”

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confidence: 99%

Electron and proton transport by NADPH oxidases

Demaurex

Petheő

2005

Phil. Trans. R. Soc. B

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The NADPH oxidase is the main weapon of phagocytic white blood cells that are the first line of defence of our body against invading pathogens, and patients lacking a functional oxidase suffer from severe and recurrent infections. The oxidase is a multisubunit enzyme complex that transports electrons from cytoplasmic NADPH to molecular oxygen in order to generate superoxide free radicals. Electron transport across the plasma membrane is electrogenic and is associated with the flux of protons through voltage-activated proton channels. Both proton and electron currents can be recorded with the patch-clamp technique, but whether the oxidase is a proton channel or a proton channel modulator remains controversial. Recently, we have used the inside-out configuration of the patch-clamp technique to record proton and electron currents in excised patches. This approach allows us to measure the oxidase activity under very controlled conditions, and has provided new information about the enzymatic activity of the oxidase and its coupling to proton channels. In this chapter I will discuss how the unique characteristics of the electron and proton currents associated with the redox activity of the NADPH oxidase have extended our knowledge about the thermodynamics and the physiological regulation of this remarkable enzyme.

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“…One of the primary means by which neutrophils destroy phagocytosed bacteria is through the production of toxic oxygen intermediates derived from superoxide anion (O -2 ), including hydrogen peroxide and hypochlorous acid (Leusen et al, 1996;Clark et al, 1987). Furthermore, the pH change resulting from the O -2 influx triggers a potassium-dependent release of proteases into the phagosome (Reeves et al, 2002).…”

Section: Productionmentioning

confidence: 99%

“…Collectively, these products kill and degrade the ingested micro-organisms. O -2 is produced by NADPH oxidase, a tightly controlled, rapidly activatable enzymic complex (Leusen et al, 1996;Clark et al, 1987). In resting neutrophils, the oxidase is inactive and its unassembled components are localized in different parts of the cell (Leusen et al, 1996;Clark et al, 1987).…”

Section: Productionmentioning

confidence: 99%

“…O -2 is produced by NADPH oxidase, a tightly controlled, rapidly activatable enzymic complex (Leusen et al, 1996;Clark et al, 1987). In resting neutrophils, the oxidase is inactive and its unassembled components are localized in different parts of the cell (Leusen et al, 1996;Clark et al, 1987). The membrane-bound components are cytochrome b 558 , which is comprised of gp91 phox and p22 phox (Parkos et al, 1987), and Rap1a (Babior, 1999).…”

Section: Productionmentioning

confidence: 99%

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Microbe-vector Interactions in Vector-borne Diseases

Gillespie¹,

Smith²,

Osbourn³

2001

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Several billion people are at daily risk of life-threatening vector-borne diseases such as malaria, trypanosomiasis and dengue, and the dark shadow of plague hovers in the few endemic foci where it waits ready to re-emerge in a deadly pandemic. The abortive attempt to control malaria in the 1960s showed us the problem that we face in eradicating vector-borne diseases. Research into these tropical diseases fell into neglect during the 1960s, but in the 1970s research was once more directed towards vectorborne diseases and more recent initiatives such as the Roll Back Malaria Campaign have kept them in the international spotlight. If we are not to repeat the mistakes of the past it will be necessary to use all of our knowledge of vector biology.cambridge university press Cambridge

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NADPH oxidase of human neutrophils. Subcellular localization and characterization of an arachidonate-activatable superoxide-generating system.

Cited by 254 publications

References 77 publications

NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology

NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology

Electron and proton transport by NADPH oxidases

Microbe-vector Interactions in Vector-borne Diseases

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